Cough is one of the most common complaints for which medical attention is sought. It can be divided into acute and chronic cough according to their duration. Acute cough, lasting less than 3 weeks, is most often due to an acute viral upper respiratory tract infection and is usually transient and self-limited. Chronic cough, always lasting 8 weeks or longer, is mainly due to one or more of three aetiologies: post-nasal drip syndrome (PNDS), asthma, and gastro-oesophageal reflux disease (GORD). It has been demonstrated that specific treatment of an established aetiology of cough is highly successful. However, nonspecific antitussive therapy aiming at suppressing the sensitivity of the cough reflex regardless of the underlying aetiology of cough, is often ineffective.
Currently available nonspecific therapy is limited by lack of effective medications and/or their unacceptable or intolerable side effects. Epidemiological data from the over-the-counter (OTC) market showed that hundreds of millions of pounds in the UK and several billion dollars in the United States were spent on cough/cold. Although over 50 antitussive drugs are used in current clinical practices, a recent study suggests that OTC antitussive drugs possess little clinically relevant efficacy. Currently the most effective nonspecific antitussive agents are opiates. Almost all opiates have antitussive activity, but only those with weak analgesic activity are generally used as antitussives. An example of this type of medicine is codeine which is suitable for the treatment of dry cough that is interfering with rest or sleep. At high doses, codeine may cause sleepiness, addiction, constipation, respiratory depression and hypotension. It should not be used during pregnancy. Thus, there is current need for more effective nonspecific antitussive agents.
A number of herbs have a rich history of use for treating coughs due to colds, bronchitis, or other mild conditions. Among those herbs that have been shown to have some cough-relieving activity are marshmallow, sundew, and coltsfoot. They have been used in many parts of the world.
Phytochemical study of traditional herbal medicine has demonstrated other types of chemical compounds also have beneficial antitussive activity with less side-effect than the above-mentioned synthetic compounds. For example, neotuberostemonine isolated from Radix Stemonae, which is the root tuber of Stemona species recognized in the Pharmacopoeia of the People's Republic of China, was demonstrated to have strong antitussive effects. Furthermore, it is believed that neotuberostemonine does not act on opiate receptors while it has an antitussive potency comparable to that of codeine. Neotuberostemonine is believed to have no side-effect associated with the action on opiate receptors.
Many phytochemical studies on Stemona species have been reported. 52 alkaloids have been isolated and identified from Radix Stemonae and they are divided into five groups and a miscellaneous group according to molecular structures. The five groups are stenine, stemoamide, tuberostemospironine, stemoamine and parvistemoline (FIG. 4). Phytochemical analysis on five species of Stemona collected from different provinces and over 30 samples of Radix Stemonae from different herbal markets in China revealed that neotuberostemonine was present in only two samples. The results suggested that neotuberostemonine is present only in isolated samples of Stemona tuberosa, not universally present in Stemona. Therefore, neotuberostemonine cannot serve as a biomarker to indicate whether an herb can be useful as an antitussive agent. Another problem is that there may not be abundant raw material available for preparing neotuberostemonine as antitussive medicine.
It is an object of the present invention to obtain another group or groups of chemical compounds more universally existing in Stemona that provide main basis for the antitussive effects observed for most Stemona species. The new type(s) of compounds is to be used to make antitussive products to relieve cough and to serve as biomarkers in assessing the quality of the herbs used for relieving cough and in searching other herbs whose antitussive activity is so far unknown.